Protecting groups in the synthesis of a wide variety of organic compounds, particularly antibiotics and oligopeptides, are essential to prevent unwanted reactions of side groups at various intermediate steps. The useful qualities of a protecting group depend upon the mildness of conditions required for its removal.
Allyl protecting groups on esters, carbonates, carbamates or cinnamyl esters can normally be removed by palladium, particularly organic soluble palladium complexes possessing a coordinating phosphine ligand. See, for example, U.S. Pat. No. 4,314,942; its corresponding EPO application with publication number 0013663; Trost, B. M. et al., J. Am. Chem. Soc., 100, 7779 (1978); and Jeffrey, P. D. et al., J. Org. Chem., 47, 587 (1982). However, none of these palladium-based deprotection methods provide means for regenerating polymer supported palladium.
Accordingly, a purpose of the present invention is to provide methods and means of substantially regenerating palladium in palladium-based deprotection of allyl esters, allyl carbonate, allyl carbamates and cinnamyl esters. Regeneration of palladium avoids the expense of using new batches repeatedly in the commercial production of a variety of compounds, e.g. antibiotics such as cefoxitin or imipenem. In addition, no loss of yield in deprotected compound results.
Furthermore, the methods of the present invention provide readily manipulable complexes of palladium, in the form of polymer supported Pd(O). These complexes are insoluble in both organic and aqueous environments, properties of commercial advantage in synthesis of a variety of compounds.
The methods of the present invention also provide mild conditions for synthesizing a wide variety of organic compounds, many of which are unstable and susceptible to inactivation during synthesis.